FDA still not happy with Kamada inhaled AAT drug

Israeli biotech Kamada has hit another hurdle in its marathon bid to bring the first inhaled treatment for alpha-1 antitrypsin (AAT) deficiency to market as an alternative to intravenous drugs.

The company, which specializes in developing drugs from plasma proteins, says the FDA is still not fully satisfied with the proposed phase 3 protocol for nebulized AAT as a treatment for AAT deficiency, and it likely won’t be able to start the trial before the end of the year as hoped. Shares in the company fell almost 10% after the announcement.

It’s not the first knockback for the program, coming after the FDA raised concerns about the safety and efficacy of the drug last year. Kamada amended its protocol to try to address those concerns but hasn’t yet satisfied the regulator sufficiently to get the green light for an Investigational New Drug (IND) application. It now says it will try again with a new filing slated for the third quarter of this year but “cannot currently anticipate if and when … discussions with the FDA will materialize into an approved IND.”

The company withdrew a European marketing authorization application for the product last year after the EMA indicated it would need an additional trial to support approval, and the FDA’s latest decision has an impact on both sides of the Atlantic, as Kamada had planned to use its new trial to support a fresh EU application.

AAT affects around 1 in 1,500 to 3,000 people in the U.S. and Europe, but is often misdiagnosed and undertreated. AAT is produced in the liver and protects the lungs from inflammation caused by infections or irritants, so one of the main symptoms is chronic obstructive pulmonary disorder. It also causes excessive levels of abnormal AAT buildup in the liver, causing damage.

Back in 2014, Kamada announced that a midstage study of inhaled AAT failed to achieve its primary endpoint of time to the first moderate or severe exacerbation event at one year, although it did achieve secondary objectives such as improvements in lung function. Since then, it has continued to develop the drug but suffered another setback when it lost Chiesi as a European partner last November.

The biotech already has an intravenous AAT formulation on the market under the trade name Glassia, which is distributed in the U.S. by Shire, as well as a handful of other products including a rabies prophylaxis product that picked up a U.S. approval last year.  

Inhaled AAT is Kamada’s lead pipeline candidate, however, and the delay leaves a gap in its plans to add to its current product portfolio, which made around $100 million in sales last year. Glassia is used to treat a few hundred patients a year, but an inhaled formulation could expand the market and according to analyst predictions might become a $200 million product.

Beyond inhaled AAT, Kamada’s pipeline consists mainly of new indications for intravenous AAT, including Type 1 diabetes, graft-versus-host disease and lung transplantation. Those are all in midstage testing, says the company.